The goal of our activity is to understand the functional role and substrates underlying plastic changes in the human central nervous system and develop novel therapeutic approaches for recovery of function following stroke. Most of our work has focused on the study of plastic changes in the human motor, somatosensory and visual systems in normal volunteers and patients with stroke. This year, we identified behavioral gains in tactile discriminative skills in one hand associated with deafferentation in the other hand. In relation to use- dependent plasticity in motor cortex, we discovered that it is possible to modulate plasticity in one body part representation by stimulation with TMS and by stimulation of adjacent body part representations by tDCS. We also developed two strategies to enhance use-dependent plasticity: by administration of pharmacological agents and also by concomitant administration of transcranial magnetic stimulation. We discovered that noninvasive brain stimulation in the form of tDCS can contribute to neurorehabilitative efforts after stroke. A project is under way to evaluate application of noninvasive brain-computer interface to control hand motions after stroke. We have advanced in the understanding of the involvement of the intact hemisphere and nonprimary motor areas (particularly dorsal premotor cortex) in recovery of motor function after stroke. Evidence suggests that theta burst stimulation (TBS), especially combined with dopaminergic agents has shown effects on the excitability of human motor cortex, suggesting it may enhance synaptic plasticity and improve motor training in healthy humans. Considering that synergy between dopaminergic modulation and TBS may show promise to produce clinical gains after stroke, we have begun a new study this year to address this hypothesis. One other techniques we are interested in investigating is whether we can enhance beneficial effects of peripheral high-frequency stimulation, (pHFS), on implicit tactile and haptic learning in chronic stroke patients by a combined application of pHFS with tDCS (pHFS+tDCS) applied to the somatosensory cortex of the affected hemisphere. This approach might identify novel strategies to enhance the functional recovery after stroke and might provide deeper insight into the mechanisms involved in these behavioral gains. On the basis of this understanding, we are starting to design and test interventions to improve motor disability after lesions in the central nervous system.